Pelacarsen for Cardiovascular Disease
Recruiting in Palo Alto (17 mi)
+107 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Novartis Pharmaceuticals
Must be taking: LDL-C lowering
Disqualifiers: Uncontrolled hypertension, Heart failure, Malignancy, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?
Study CTQJ230A12303 is a randomized, double-blind placebo-controlled, Phase IIIb study to evaluate the efficacy, safety and tolerability of pelacarsen (TQJ230) 80 mg s.c. QM compared with placebo s.c. QM in US Black/African American and Hispanic participants with established ASCVD and elevated levels of Lp(a) who are treated for cardiovascular (CV) risk factors according to local practice/guidelines for the reduction of cardiovascular risk.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications. However, you must be on stable therapy for cardiovascular risk factors like LDL-C, blood pressure, and diabetes according to local guidelines.
What makes the drug Pelacarsen unique for treating cardiovascular disease?
Pelacarsen is unique because it is a liver-targeted antisense oligonucleotide specifically designed to lower lipoprotein(a) [Lp(a)] levels, which are a genetic risk factor for cardiovascular disease. Unlike other treatments, it directly targets the LPA gene messenger RNA, offering a novel approach to reducing cardiovascular risk in patients with high Lp(a) levels.12345
Research Team
NP
Novartis Pharmaceuticals
Principal Investigator
Novartis Pharmaceuticals
Eligibility Criteria
This trial is for US Black/African American and Hispanic individuals aged 18 to 80 with high Lp(a) levels and existing cardiovascular disease. They must be on stable standard treatments for other risk factors like LDL cholesterol, blood pressure, and diabetes.Inclusion Criteria
Lp(a) ≥ 125 nmol/L at the screening visit, measured at the Central laboratory
I am a Black/African American or Hispanic person aged 18 to 80 living in the US.
I am on stable treatment for cholesterol, blood pressure, or diabetes.
See 1 more
Exclusion Criteria
Pregnant or nursing women
My blood pressure is not controlled by medication.
Platelet count <140,000 per mm3
See 5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive pelacarsen (TQJ230) 80 mg s.c. QM or placebo for 52 weeks
52 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Pelacarsen (TQJ230) (Antisense Oligonucleotide)
Trial OverviewThe study tests the effectiveness of Pelacarsen (TQJ230), a medication given as an injection once a month, against a placebo in reducing cardiovascular risk by lowering Lp(a) levels in participants.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: TQJ230Experimental Treatment1 Intervention
TQJ230 80mg QM s.c.
Group II: PlaceboPlacebo Group1 Intervention
Matching placebo.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Valley Clinical Trials IncCovina, CA
Cardiology and Medicine Clinic, PALittle Rock, AR
Excel Medical Clinical Trials LLCBoca Raton, FL
C and A Clinical TrialsCape Coral, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Novartis Pharmaceuticals
Lead Sponsor
Trials
2963
Patients Recruited
4,275,000+
Founded
1996
Headquarters
Basel, Switzerland
Known For
Precision medicine
Top Products
Gleevec, Cosentyx, Entresto, Kisqali
References
The role of antisense oligonucleotide therapy against apolipoprotein-CIII in hypertriglyceridemia. [2018]Increased triglyceride levels (higher than ∼1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apo-CIII) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. While loss of function mutations in the gene encoding apo-CIII (APOC3) are associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD), overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apo-CIII concentrations), there are many patients who still have severe hypertriglyceridemia and are at risk for pancreatitis and potentially CVD. The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apo-CIII production and triglyceride concentrations and is being currently evaluated in phase 3 trials. In this narrative review we present the currently available clinical evidence on the efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.
Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease. [2023]Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular disease (CVD) and statins may not be protective in advanced CKD. The reasons for the limited efficacy of statins in advanced CKD are unclear, but statins may increase plasma levels of the highly atherogenic molecule lipoprotein(a), also termed Lp(a), as well as PCSK9 (protein convertase subtilisin/kexin type 9) levels. Lp(a) has also been linked to calcific aortic stenosis, which is common in CKD. Moreover, circulating Lp(a) levels increase in nephrotic syndrome with declining renal function and are highest in patients on peritoneal dialysis. Thus, the recent publication of the Phase 2 randomized controlled trial of pelacarsen [also termed AKCEA-APO(a)-LRx and TQJ230], a hepatocyte-directed antisense oligonucleotide targeting the LPA gene messenger RNA, in persons with CVD should be good news for nephrologists. Pelacarsen safely and dose-dependently decreased Lp(a) levels by 35-80% and a Phase 3 trial [Lp(a)HORIZON, NCT04023552] is planned to run from 2020 to 2024. Unfortunately, patients with estimated glomerular filtration rate <60 mL/min or urinary albumin:creatinine ratio >100 mg/g were excluded from Phase 2 trials and those with 'significant kidney disease' will be excluded from the Phase 3 trial. Optimized exclusion criteria for Lp(a)HORIZON would provide insights into the role of Lp(a) in CVD in CKD patients.
Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects. [2023]Pelacarsen is a liver-targeted antisense oligonucleotide that potently lowers lipoprotein(a) [Lp(a)] levels. Its safety and efficacy in diverse populations has not been extensively studied.
Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials. [2023]An increase in blood lipoprotein (a) [Lp(a)] levels, mostly genetically determined, has been identified as an independent risk factor of atherosclerotic cardiovascular disease. No drug has yet been approved that markedly lowers Lp(a) and thereby reduces residual cardiovascular risk. The aim of this article was to critically review the evidence from clinical development studies to date on the efficacy and safety of new RNA-based therapeutics for targeted lowering of Lp(a). PubMed/MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched without any language or date restriction up to November 5, 2022, and a total of 12 publications and 22 trial records were included. Several drugs were found that are currently in various stages of clinical development, such as the antisense oligonucleotide pelacarsen and the small interfering RNA molecule olpasiran and drugs coded as SLN360 and LY3819469. Among them, pelacarsen has progressed the most, currently reaching phase 3. All these drugs have so far shown satisfactory pharmacokinetic properties, consistently high and stable, dose-dependent efficacy in lowering Lp(a) even by more than 90%, with an acceptable safety profile in subjects with highly elevated Lp(a). In addition, reports of early clinical trials with pelacarsen imply a promising suppressive effect on key mechanisms of atherogenesis. Future research should focus on confirming these beneficial clinical effects in patients with lower average Lp(a) levels and clearly demonstrating the association between lowering Lp(a) and reducing adverse cardiovascular outcomes.
A Review of the Clinical Pharmacology of Pelacarsen: A Lipoprotein(a)-Lowering Agent. [2022]Patients with genetically associated elevated lipoprotein(a) [Lp(a)] levels are at greater risk for coronary artery disease, heart attack, stroke, and peripheral arterial disease. To date, there are no US FDA-approved drug therapies that are designed to target Lp(a) with the goal of lowering the Lp(a) level in patients who have increased risk. The American College of Cardiology (ACC) has provided guidelines on how to use traditional lipid profiles to assess the risk of atherosclerotic cardiovascular disease (ASCVD); however, even with the emergence of statin add-on therapies such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, some populations with elevated Lp(a) biomarkers remain at an increased risk for cardiovascular (CV) disease. Residual CV risk has led researchers to inquire about how lowering Lp(a) can be used as a potential preventative therapy in reducing CV events. This review aims to present and discuss the current clinical and scientific evidence pertaining to pelacarsen.